Sugar junkies: Melanoma cells found to be addicted to glucose, offering new treatment hope

Researchers at Melbourne’s Peter MacCallum Cancer Centre have revealed melanoma cells are dependent on glucose to grow and spread, opening the door to the development of new therapies focused on blocking glucose use.

In a paper published today in Cancer Discovery, the academic journal of the American Association for Cancer Research, the research team found that melanomas driven by mutations in the BRAF gene, comprising 40 per cent of all melanoma cases, rely on glucose as readily available fuel to drive their aggressive growth.

Professor Rod Hicks: Director, Centre for Cancer Imaging at Peter Mac says the laboratory research project, supported with a project grant from Cancer Council Victoria, was prompted by clinical diagnostic PET/CT scans — used to monitor the metabolic activity of melanomas during treatment — which showed that, almost immediately after the start of treatment, melanoma cells stop drawing in glucose but don’t necessarily die.

‘Malignant melanoma cells are among the most intensely bright tumours when scanned with PET imaging, suggesting they have a strong appetite for glucose to support cell growth.

‘We previously thought the reduction in glucose uptake by melanoma was a result of cell death caused by cancer treatments; we have now found most cells actually die as a result of being starved of glucose, while a small number manage to find a way to survive.’

Professor Grant McArthur: Chair, Melanoma and Skin Service and Head, Cancer Therapeutics Program at Peter Mac says research efforts will now concentrate on mechanisms of resistance; the genomic changes in melanoma that allow tumours to survive a ‘drought’ of blocked glucose use.

‘Targeted therapies in melanoma have provided months and, in some cases, years of high-quality life to people with advanced disease — which is generally around eight months if untreated — but these patients invariably relapse over time, as melanoma cells either find alternative fuels, or enter a “self-eating” phase, similar to the manner in which a person’s body breaks down fat and muscle to survive starvation, before finding ways to turn their fuel source back on.

‘This vulnerable stage, when melanoma cells are overcoming their sugar addiction, presents an attractive target for new treatments, and we’re investigating combination therapies to eradicate cancer cells that are managing to survive, even when their fuel source is cut off.’

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Full study here:  

Response of BRAF-Mutant Melanoma to BRAF Inhibition Is Mediated by a Network of Transcriptional Regulators of Glycolysis

http://cancerdiscovery.aacrjournals.org/

Graham